How should I interpret a low white blood cell count, low red blood cell count, low hemoglobin and hematocrit with normal mean corpuscular volume, low mean corpuscular hemoglobin concentration and high red cell distribution width, and what workup and treatment are recommended?

Interpretation and Management of Mild Normocytic Anemia with Leukopenia and Elevated RDW

This patient presents with mild normocytic anemia (hemoglobin 11.8-12.7 g/dL, low but stable), borderline low WBC (3.4-4.1 K/μL), normal MCV (83.9-91.7 fL), and persistently elevated RDW (17.0-18.4%), which represents a multi-lineage cytopenia pattern requiring hematology consultation to exclude bone marrow dysfunction, even though iron deficiency remains the most likely diagnosis. 1

Critical Initial Assessment

The presence of abnormalities in two cell lines (anemia and leukopenia) mandates careful evaluation and likely warrants discussion with a hematologist. 1 You should not presume iron deficiency alone explains both cytopenias without excluding more serious pathology. 1

Key Laboratory Pattern Recognition

The combination of findings suggests:

• Mild normocytic anemia: Hemoglobin 11.8-12.7 g/dL (reference 13.2-17.1 g/dL) with normal MCV (83.9-91.7 fL) indicates this is not yet microcytic, though trending toward lower MCV values over time 1, 2
• Elevated RDW (17.0-18.4%): This reflects heterogeneous red cell populations and is characteristic of evolving iron deficiency or mixed nutritional deficiencies 1, 3, 4
• Borderline leukopenia (3.4-4.1 K/μL): This is NOT explained by iron deficiency and requires separate investigation 1

Immediate Diagnostic Workup Required

First-Line Iron Studies (Highest Priority)

Complete iron deficiency workup immediately, including serum ferritin and transferrin saturation (TSAT), as these are the most powerful tests for confirming iron deficiency. 1

• Serum ferritin: Ferritin <30 μg/L confirms iron deficiency in the absence of inflammation; ferritin <15 μg/L is diagnostic 1
• Transferrin saturation: TSAT <15-20% supports iron deficiency and is less affected by inflammation than ferritin 1
• Absolute reticulocyte count: Evaluates bone marrow response; low or normal count indicates impaired red cell production 1

Additional Essential Tests

• Vitamin B12 and folate levels: To exclude combined deficiency that could explain the elevated RDW 1
• Comprehensive metabolic panel: To assess renal function and electrolytes
• Peripheral blood smear: To evaluate red cell morphology and white cell differential

Red Flag Evaluation for Bone Marrow Pathology

The leukopenia combined with anemia raises concern for conditions such as:

• Aplastic anemia: Most patients with severe aplastic anemia exhibit normocytic anemia with significantly decreased WBC, though some non-severe cases can present with macrocytic anemia and elevated RDW 3
• Myelodysplastic syndrome: Typically presents with macrocytic anemia and elevated RDW (84.7% have increased RDW), though this is less likely given the normal MCV 3
• Bone marrow infiltration or dysfunction: Requires exclusion before attributing findings to nutritional deficiency alone 1

Clinical Significance of Elevated RDW

The persistently elevated RDW (17.0-18.4%) in this patient is clinically significant. 3, 4 In aplastic anemia studies, patients with elevated RDW had significantly higher WBC, absolute neutrophil count, platelets, and reticulocytes compared to those with normal RDW, suggesting better residual bone marrow hematopoietic function but more severe anemia. 3 This pattern may indicate evolving iron deficiency with active erythropoiesis attempting to compensate. 4, 5

Management Algorithm

If Iron Deficiency is Confirmed:

1. Initiate oral iron supplementation: Ferrous sulfate 325 mg (65 mg elemental iron) 1-3 times daily between meals 1
2. Monitor response: Expect hemoglobin increase of approximately 1-2 g/dL every 2-4 weeks 1
3. Continue treatment: Iron for 3-6 months after hemoglobin normalizes to replenish stores 1
4. Investigate underlying cause: Detailed menstrual history (if female), dietary assessment, and consideration of gastrointestinal evaluation if losses do not explain severity 1

Concurrent Leukopenia Evaluation:

Do not overlook the leukopenia—this is not explained by iron deficiency alone and requires separate evaluation. 1 Consider:

• Benign ethnic neutropenia: Particularly relevant in certain populations where ANC may be constitutionally lower 6
• Viral suppression: Recent or chronic viral infections
• Medication effects: Review all current medications
• Nutritional deficiencies: B12/folate deficiency can affect multiple cell lines
• Primary bone marrow disorder: If other causes excluded

Common Pitfalls to Avoid

• Do not accept ferritin alone in patients with inflammation: Use TSAT to confirm iron deficiency 1
• Do not rely on MCV alone: Iron deficiency can present with normal MCV in early stages 1
• Do not presume dietary insufficiency as the sole cause: Confirm with iron studies and exclude other pathology 1
• Do not ignore the multi-lineage cytopenia: This pattern requires hematology consultation even if iron deficiency is confirmed 1
• Do not use outdated reference ranges: Laboratory values vary by race, gender, and age; normal hemoglobin can be as low as 9.6 g/dL in Black women 6

When to Refer to Hematology

Immediate hematology consultation is warranted if:

• Iron studies do not confirm iron deficiency as the sole explanation
• No response to iron supplementation after 4-6 weeks
• Leukopenia worsens or additional cytopenias develop
• Any concerning findings on peripheral blood smear
• Patient develops symptoms suggesting bone marrow failure (infections, bleeding, fatigue out of proportion to anemia)